Cannabis-based therapeutic product for treatment of chronic pain

ABSTRACT

A  cannabis  based therapeutic product for treatment of chronic pain produced by separating hash resin from plant material of the  cannabis  plant, pressing the hash resin to expel oil, leaving spent hash resin, extracting further cannabinoids from the spent hash resin using MCT oil, separating the  cannabis  compounds from the oils using high pressure liquid chromatography, flash chromatography, or similar techniques, and processing selected  cannabis  compound formulations into a pill, tablet, liquid, or other form suitable for administration as a therapeutic product for treatment of chronic pain, optionally with the further step of enriching the product with a formulation comprising at least 1% by weight purified -myrcene, prior to processing into a final product.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of, and priority to, U.S. provisionalpatent application 62/638,238, titled “CANNABIS-BASED THERAPEUTICPRODUCT FOR TREATMENT OF CHRONIC PAIN”, filed on Mar. 4, 2018, and isalso a continuation-in-part of U.S. patent application Ser. No.15/616,802, titled “DEVICE FOR DELIVERY OF SMOKABLE CANNABIS ANDMANUFACTURING METHOD FOR SAME”, filed on Jun. 7, 2017, and is also acontinuation-in-part of U.S. patent application Ser. No. 15/615,829,titled “SYSTEM AND METHOD ENHANCED CANNABINOID EFFECT DELIVERY”, filedon Jun. 6, 2017, the entire specifications of each of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention is in the field of cannabis active compoundformulation for medicinal application. Specifically, the use offormulations containing cannabis-derived compounds as medical treatmentsfor chronic pain.

Discussion of the State of the Art

Recently, multiple states have passed legislation legalizing cannabisfor medical usage. This change promises to greatly increase not only themarket for cannabis, but also the research into further medicinallyimportant effects of cannabis compounds, and the discovery of ways tooptimize the effects of known and newly discovered cannabis compoundsfor medical use.

There is a large body of anecdotal evidence that cannabis, particularlysmoked cannabis plant matter, provides substantial relief from chronicpain caused by numerous chronic health conditions such as cancer,multiple sclerosis, arthritis, nerve damage, back pain, fibromyalgia,and similar conditions. These conditions are often resistant to standardtreatments, even treatment with opioid medications such as morphine. Asubstantial body of medical literature supports the anecdotal evidencethat cannabis compounds can provide relief from chronic pain. However,of the several cannabis-based products on the market (ajulemic acid,Cannador®, Marinol®, Cesamet®) that have been studied for their use intreatment of pain, most were developed to treat other symptoms ofchronic illness, and most have exhibited modest pain relief, at best.One product, Sativex®, is a cannabis-derived oromucosal spray containingequal portions of THC and CBD which has been shown in clinical studiesto provide relief from chronic pain. It was approved in Canada in 2005for treatment of central neuropathic pain in multiple sclerosis, and in2007 for intractable cancer pain. However, there are many other medicalconditions for which cannabis-based products may be useful in treatingchronic pain.

What is needed is a product that provides these cannabis compounds in aform suitable for use as medications and therapies for pain, especiallypain caused by chronic conditions such as cancer, multiple sclerosis,arthritis, nerve damage, back pain, fibromyalgia, and similarconditions, and especially where such pain is resistant to standardforms of treatment.

SUMMARY OF THE INVENTION

Accordingly, the inventor has conceived and reduced to practice, in apreferred embodiment, a plurality of formulations for cannabinoidmedical and therapeutic benefits. The cannabinoid, terpene, andflavonoid formulations used according to aspects of the invention areintended to mitigate at least one medical issue. For example, the twomain cannabinoids in the cannabis plant, −9-tetrahydrocannabinol (THC)and cannabidiol (CBD) are known to have analgesic effects by themselves,and may also serve to complement the pain-reliving effects of opioidmedications commonly used as a treatment for chronic pain. As anotherexample, the terpene myrcene has analgesic effects, and also increasesthe permeability of the blood-brain-barrier to other terpenes,cannabinoids, and flavonoids which raises the saturation level of atleast one cannabinoid receptor, such as CB1, within the human body.Various formulations of cannabinoids, terpenoids, and flavonoids couldbe tailored to produce the desired pain-relieving effects for variousclasses of chronic pain, and may also provide additional benefits suchas control of inflammation, which further reduces chronic pain anddiscomfort.

According to a preferred embodiment, the formulation is compounded intoa pill or tablet form, or in a sublingual spray, and is administeredorally.

According to another preferred embodiment, the formulation is compoundedinto a liquid form suitable for inhalation using a vaporizer.

BRIEF DESCRIPTION OF FIGURES

The accompanying drawings illustrate several embodiments and, togetherwith the description, serve to explain the principles of the inventionaccording to the embodiments. It will be appreciated by one skilled inthe art that the particular embodiments illustrated in the drawings aremerely exemplary, and are not to be considered as limiting of the scopeof the invention or the claims herein in any way.

FIG. 1 is a method diagram illustrating a process 100 for preparingcannabis medicinal products, according to an embodiment.

FIG. 2 is a method diagram illustrating a process for preparing anenhanced smokable therapeutic cannabis product using hash resin,according to a preferred embodiment.

DETAILED DESCRIPTION

Headings of sections provided in this patent application and the titleof this patent application are for convenience only, and are not to betaken as limiting the disclosure in any way.

Cannabis has been extensively cultivated throughout the world forcenturies. Worldwide effects-targeted cultivation has progressed to thepoint where there are hundreds, if not thousands, of cultivars orstrains which contain differing levels of the many active compounds thatgive cannabis its wide range of sought-after medical effects. One familyof active compounds that are specific to cannabis is the cannabinoidfamily, of which more than 80 have been identified that may haveoverlapping but different medical effect profiles. These have beenfurther separated into subclasses comprising: tetrahydrocannabinols(THC); cannabidiols (CBD); cannabichromenes (CBC); cannabinol (CBN);cannabigerols (CBG); cannabinodiol (CBDL); and other cannabinoids(cannabicyclol (CBL), cannabielsoin (CBE), cannabitriol (CBT) and othermiscellaneous types.

In raw cannabis, the cannabinoids within the flowers' trichomes arecarboxylated, meaning they have a COOH carboxylic acid group in theirstructure. These are mildly, if at all, psychoactive. In order for thereto be psychoactivity the cannabinoids must be decarboxylated, or“decarbed” in layman's terms. Non-psychoactive THCA, for example, isdecarboxylated to THC, a psychoactive cannabinoid. Both drying (oraging) and heat accomplish this chemical reaction, but the applicationof heat also results in the loss of certain other cannabis componentssuch as the terpenes, which are highly volatile. Both the decarboxylatedcannabinoids and the carboxylated cannabinoids exhibit importanttherapeutic effects for health, and although one can be chemicallyconverted into the other, carboxylated cannabinoids becomingdecarboxylated cannabinoids, As used herein both will be referred to assimply cannabinoids.

The biological effects of the cannabinoids may be mediated through tworeceptors specific for a class of endogenous cell signaling molecules,such as but not limited to N arachidonoylethanolamine also known as AEAor anandamide, a neurotransmitter that predominantly binds to thecannabinoid receptor CB1 and a second compound, 2-arachidonoylglycerolalso known as 2-AG which predominantly binds to the CB2 receptor.Expression of the CB1 receptor is found at highest levels in the centralnervous system of humans and animals, particularly in the hippocampus,basal ganglia, neocortex, and spine (although expression in peripheralorgans such as but not limited to the peripheral nervous system, liver,intestines, and kidneys is also present). Activation of the CB1 receptorhas been linked to feelings of euphoria and an increase in appetite,among other effects. Expression of the CB2 receptor is found in thecentral and peripheral nervous system, the immune system and immuneresponse-related cells, and peripheral organs, among other areas ofexpression. Activation of the CB2 receptor may have an analgesic effect,reduce inflammation, and increase of immune response towards certainpathogenic bacteria and fungi. The CB2 receptor may also mediateanti-cancer effects attributed to cannabinoids. Most recently, inrelation to the CB2 receptor, it has been determined that differentligand agonists may specifically or predominantly activate specificreceptor responses indicating a level of ligand functional selectivityfor effects linked to the receptor.

Other cannabinoid receptors are found in almost every organ of the bodyincluding the skin, the digestive tract, and even in the reproductiveorgans. Cannabinoid receptors interact with cells in a lock (the cellreceptor) and key (the cannabinoid) type of mechanism. The combinationof the cell receptors and the cannabinoids comprise the endocannabinoidsystem, or ECS, which is an intricate network of cell receptor proteinsthat perform various functions in the body, and is considered to be thegreatest neurotransmitter system in the body. Bearing this in mind, itbecomes important to realize and understand how cannabis can have animpact on numerous health issues including, but not limited to,Alzheimer's disease, memory loss, multiple sclerosis (MS) and otherneurodegenerative diseases, and pain control and relief.

The major differences between the various cannabinoids are determined bythe extent to which they are psychologically active (psychoactive).Three substantial classes of cannabinoids, including the cannabigerols(CBGs), cannabichromenes (CBCs), and cannabidiols (CBDs), are not knownto have psychoactive effects. −9-tetrahydrocannabinol (THC), cannabinol(CBN), and some other cannabinoids are known to be psychoactive tovarying degrees. Non-psychoactive CBD is likely the most abundantcannabinoid, contributing up to 40% of cannabis resin in some strains(particularly those referred to as hemp strains); CBD has also beenimplicated in lessening the psychoactive effects of THC.

Of the over 80 known cannabinoid species, those most prevalent and moststudied in cannabis cultivars are:

THC—9-tetrahydrocannabinol

CBD—cannabidiol

CBC—cannabichromene

CBN—cannabinol

CBG—cannabigerol

THCv—tetrahydrocannabivarin

CBDv—cannabidivarin

−8-THC—−8-tetrahydrocannabinol

THCA—−9-tetrahydrocannabinolic acid

CBDA—cannabidiolic acid

A number of these 80-plus cannabinoids display a plurality of importantmedical effects. The subset of the aforementioned cannabinoids for whichthese medically beneficial effects are characterized and confirmed arepresented here with their chemical formulae and structures.

THC:

As used herein, THC refers to −9-tetrahydrocannabinol, the chemicalformula for which is C₂₁H₃₀O₂ and the structure of which is:

THC is recognized as the primary psychoactive compound in cannabis andis the most common cannabinoid. Along with its psychoactive properties,THC may be medically used to alleviate several types of pain includingthe nerve-related pain of diabetic neuropathy and multiple sclerosis.Additionally, THC may be effective in alleviation of the symptoms ofPTSD and reduction of nausea and vomiting, particularly that caused bychemotherapy. It has been shown to aid those with anorexia, as well ascancer and HIV associated wasting syndrome as it is an appetitestimulant. It improves breathing for asthmatics, acting as a potentbronchodilator, it relieves eye pressure in patients with glaucoma,improves insomnia, sleep apnea, and reduces nightmares. THC aids thosewith inflammatory bowel diseases such as Crohn's disease, ulcerativecolitis and leaky gut, as well as other intestinal diseases bydecreasing intestinal permeability and strengthening intestinal tightjunctions. THC slows and prevents Alzheimer's disease and helps controlseizures. THC reduces pain and tremors and improves sleep for those withParkinson's disease. THC, CBD, CBG, and CBC together worksynergistically as a powerful cancer tumor-fighting combination. Thiscombination is more powerful than any single one of these working alone.

CBD:

As used herein, CBD stands for cannabidiol, the chemical formula forwhich is C₂₁H₃₀O₂ and the structure of which is:

CBD, or cannabidiol, is a non-psychoactive member of the cannabinoidsand is one of the most prevalent chemical compounds in the cannabisplant. Found predominantly in the resin glands of the female plant, thiscompound can stop muscle spasms and epileptic seizures, and can reduceidiopathic anxiety, a prevalent and significantly debilitating aspect ofmental illness. It is used to treat nicotine addiction, osteoporosis,diabetes, cancer, obsessive-compulsive disorder, Lupus, Parkinson'sdisease, and motor disorders, and soothes neuropathic and chronic pain.It has anti-inflammatory, antioxidant, neuroprotectant, anxiolytic,antidepressant, analgesic, anti-tumor, and anti-psychotic effects. CBDis powerful all by itself, but it is even more powerful when combinedwith other cannabinoids such as THC.

CBC:

As used herein, CBC stands for cannabichromene, the chemical formula forwhich is C₂₁H₃₀O₂ and the structure of which is:

Cannabichromene, or CBC, is the third most prevalent cannabinoid in themarijuana plant in general. In some strains CBC is more prevalent thanCBD, and like CBD it is non-psychoactive.

CBC is anti-inflammatory and even more so when combined with THC. It hasanti-tumor effects and shows promise in fighting breast cancer. Whencombined with CBD, THC, and CBG, the cancer fighting effects areintensified. It may be useful as an antidepressant and may be morepowerful than the other cannabinoids in this capacity. CBC showsantiviral and mild antifungal activity. While CBC addresses severalother health issues, including inflammation, cancer, depression, andfungal infections, it also increases the number of brain cells andtherefore is useful in the treatment of several brain related disorders.CBC promotes neurogenesis in individuals at any age. This not onlyaffects memory and learning, but can off-set certain dementias whichoccur when the brain stops growing new cells. It is likely that CBC canalleviate to some extent certain forms of depression andneuro-degenerative diseases via this particular mechanism ofneurogenesis.

CBN:

As used herein, CBN stands for cannabinol, the chemical formula forwhich is C₂₁H₂₆O₂ and the structure of which is:

Cannabinol, or CBN, emerges when the dried cannabis flower becomesstale; over time, THC and CBD, which are generated byenzymatically-driven synthesis from CBG, break down through oxidativedegeneration into CBN. CBN has antibiotic properties, including againstmethicillin-resistant Staphylococcus aureus (MRSA), and also haspain-relieving properties through the release of endorphins. It maydelay the onset of, and relieve symptoms of, degenerative motor neuraldiseases such as amyotrophic lateral sclerosis (ALS) and MS. It works asan appetite stimulant and is more powerful than CBD and CBG in thisregard. It has been found to have potent sedative characteristics,making it possibly the most potent single sedative of all thecannabinoids. When combined with THC, CBN has also been found to beeffective at lowering the ocular pressure which produces blindness inglaucoma patients. CBN also promises to be useful in future for loweringblood pressure overall.

CBG:

As used herein, CBG stands for cannabigerol, the chemical formula forwhich is C₂₁H₃₂O₂ and the structure of which is:

CBG, or cannabigerol, is found in cannabis early in the growth cycle,making it somewhat difficult to find in large quantities (CBG issynthesized from smaller constituents, and serves as the feedstock forenzymatic synthesis of THC, CBD, and other cannabinoids, and so CBG isregarded as the source of all cannabinoids. It is non-psychoactive andcan also be cultivated in hemp, in which it occurs in greaterquantities. CBG has antibiotic properties stronger than CBN andcomparable to CBD and is effective against various types of bacteria andfungi. It has therapeutic potential for skin conditions like psoriasisand eczema. CBG is reportedly a more potent pain reliever than THC, andfunctions as an antidepressant and mood-stabilizer by preventing theuptake of GABA and by increasing serotonin levels in the brain.

THCV:

As used herein, THCV stands for tetrahydrocannabivarin, the chemicalformula for which is C₁₉H₂₆O₂ and the structure of which is:

THCV, or tetrahydrocannabivarin, is one of the several cannabinoids thatworks in synergy with THC, and mitigates some of the negativepsychoactive impacts of THC. THCV's medical uses are antiepileptic,anticonvulsant, and anti-seizure; it is neuroprotective and mitigatessome of the short-term memory and speech impairment that comes from THC;it promotes weight loss by suppressing the appetite and possiblydecreasing body fat and boosting energy metabolism.

CBDV:

As used herein, CBDV stands for cannabidivarin, the chemical formula forwhich is C₁₉H₂₆O₂ and the structure of which is:

Cannabidivarin, or CBDV, is a slightly-degraded close relative of CBD.It is used as an anticonvulsant, an antiepileptic, and has antiemeticproperties (as well as aiding those with gastrointestinal issues).

−8-THC:

As used herein, −8-THC stands for −8-tetrahydrocannabinol, the chemicalformula for which is C₂₁H₃₀O₂ and the structure of which is:

−8-tetrahydrocannabinol is different from −9-tetrahydrocannabinol inthat it is less psychoactive. It has both neuroprotective andanti-anxiety properties, as well as being anti-emetic, and may be astronger appetite stimulant than −9-THC, making it an importantconsideration for people undergoing chemotherapy.

THCA:

As used herein, THCA stands for −9-tetrahydrocannabinolic acid, thechemical formula for which is C₂₂H₃₀O₄ and the structure of which is:

−9-tetrahydrocannabinolic acid, or THCA, is a non-psychoactive compoundfound in cannabis prior to decarboxylation to the psychoactive version,THC, by application of heat or drying or both. THCA levels areparticularly high in the live or freshly harvested plant, but as theplant dries, THCA slowly converts to THC, a process expedited by smokingor vaping. Because THCA readily converts to the psychoactive THC uponheat application such as smoking or vaping, it cannot be inhaled orabsorbed into the body by these particular means. THCA showsanti-inflammatory properties and may thus be used in treatment ofarthritis and lupus. Its neuroprotective properties may make THCA acandidate for treatment of neurodegenerative diseases; its anti-emeticproperties making it a possible treatment for nausea and appetite loss,and its anti-proliferative properties making it a candidate in treatmentin certain cancers such as but not limited to prostate cancer.

CBDA:

As used herein, CBDA stands for cannabidiolic acid, the chemical formulafor which is C₂₂H₃₀O₄ and the structure of which is:

Cannabidiolic acid, or CBDA, cannot administered by smoking orvaporizing because doing so decarboxylates it to CBD, similar to THCAconversion to THC. The therapeutic uses for CBDA include antibacterial,anti-emetic, anti-inflammatory, and cancer cell anti-proliferative.

Another family of active compounds present in, but not exclusive to,cannabis are the terpenes and decarboxylated terpenes, which are knownas terpenoids. Decarboxylation occurs with the removal of the COOHfunctional group, and can be seen in drawings of the structures. Thesetwo terms are commonly used interchangeably, and although they are notchemically identical in structure or chemical formula as terpenoids aredecarboxylated versions of some terpenes and exist in plants in thisdecarboxylated form, for the purposes of this invention both will bereferred to as simply terpenes. Though cannabis contains up to 200different terpenes and terpenoids, there are approximately 10 primaryterpenes and 20 secondary terpenes that occur naturally in significantconcentrations in the cannabis plant.

Terpenes are vital components of cannabis, and are important medicinallyactive compounds that are found in up to 1.5% of the total extraction.They are a large and diverse class of organic compounds, produced by awide variety of plants giving them their flavor, aroma, and color.Terpenes are the building blocks of a plant's essential oils, andessential oils contain mixtures of the various terpenes found in theplants from which they were extracted.

The isoprene skeleton (C₅Hs) may be found in naturally occurringterpenes (also known as isoprenoids), but these terpene compounds do notarise from isoprene itself. Terpenes may be thought of as multiples ofisoprene subunits, which is the cornerstone of the “isoprene rule” forterpenes.

The ten primary terpenes and twenty secondary terpenes that occur insignificant concentrations are as follows:

The primary terpenes are: myrcene, -pinene, ocimene, terpineol,-caryophyllene, linalool, limonene, terpinolene, valencene, andgeraniol.

The secondary terpenes are: phellandrene, carene, terpinene, fenchol,borneol, bisabolol, phytol, camphene, sabinene, camphor, isoborneol,menthol, cedrene, nerolidol, guaiol, isopulegol, geranyl acetate,cymene, eucalyptol, and pulegone.

These terpenes have non-psychoactive therapeutic effects and may besafely used to treat a variety of health conditions. They may also becombined with each other and with cannabinoids, yielding a whole newrange of health effects. Some combinations of terpenes act in synergywith boosting effects, while others act as antagonists with effects thatinhibit. Some terpenes increase the assimilation of THC, while othersmay affect the flow of dopamine and serotonin, two of the mainregulators of mood and behavior.

Cannabinoid-terpenoid interactions have the potential to produce synergywith respect to the treatment of pain, inflammation, depression,anxiety, addiction, mood and behavior, epilepsy, cancer, fungalinfections and bacterial infections, including MRSA.

The primary and secondary terpenes with some of their medical actionsare as follows:

Myrcene—Myrcene, specifically -myrcene, is a monoterpene and the mostcommon terpene produced by cannabis (some varieties contain up to 60%-myrcene as a fraction of the total terpene content). -myrcene is notfound in nature, and was first synthesized in 1965. The chemical formulafor -myrcene is C₁₀H₁₆ and the structure is:

Myrcene is found in most varieties of cannabis as well as menthol, lemongrass, and hemp, and is widely used in the perfume industry. Its aromahas been described as musky, earthy, and herbal.

Myrcene has some very special medicinal properties, including loweringthe resistance across the blood-brain barrier allowing itself and manyother chemicals to cross the barrier more easily and quickly. Myrcenealso increases cell membrane permeability, and in the case ofcannabinoids like THC, -myrcene allows the cannabinoid to take effectmore quickly. More uniquely still, -myrcene has been shown to increasethe maximum saturation level of the CB1 receptor, allowing for a greatermaximum psychoactive effect. Myrcene has anti-microbial and anti-septicproperties, and acts as a natural anti-depressant, anti-carcinogen andanti-inflammatory agent. It is a potent analgesic, and isanti-mutagenic. It blocks the action of cytochrome, aflatoxin B andother pro-mutagenic carcinogens. It acts as an inhibitor of gastric andduodenal ulcers. Its sedative and relaxing effects make it ideal for thetreatment of insomnia and pain.

-Pinene—Alpha-pinene is a monoterpene alkene isolated from pine needleoil as well as from cannabis. There are two structural isomers of pinenefound in nature: -pinene and -pinene, with -pinene being the most widelyencountered terpenoid in nature. With an aroma and flavor of pine, thisis partially where pine trees get their scent. The chemical formula isC₁₀H₁₆ and the structure is:

Pinene is one of the principal monoterpenes that is importantphysiologically in both plants and animals. It tends to react with otherchemicals, forming a variety of other terpenes (like limonene), as wellas other compounds.

Medicinally, -pinene has an anti-tumor effect and has shown anti-canceractivity. Alpha-pinene is used as an anti-inflammatory, expectorant,bronchodilator, memory enhancer, as a local antiseptic, and it maydecrease oil production in oily skin. It acts as a broad spectrumantibiotic and is highly effective against MRSA when combined with thecannabinoids CBD and CBN, all three working in synergy with each other.Alpha-pinene increases alertness and counteracts some of the negativeeffects of the cannabinoids THC, such as anxiety. It is also believedthat the negative memory effects of THC may be lessened if mixed with-pinene.

Ocimene—Ocimene is a group of isomeric monoterpenes found in a widevariety of fruits, spices, and plants. Alpha-ocimene and the two-ocimenes, cis-ocimene and trans-ocimene, differ in the position of theisolated double bond: in the alpha isomer it is terminal. -ocimeneexists in two stereoisomeric forms, cis and trans, with respect to thecentral double bond. Ocimene is often found naturally as a mixture ofits various forms. The chemical formula is C₁₀H₁₆ and the threestructures are:

Ocimene is recognized by its sweet, fragrant, herbaceous, and woodsyaromas, which feature prominently in several perfumes as well asflavorings, and which help plants defend themselves in their naturalenvironment. Ocimene occurs naturally in botanicals as diverse ascannabis, mint, parsley, pepper, basil, mangoes, orchids, kumquats, andallspice.

Ocimene's potential medical benefits include: antiviral, antifungal,antiseptic, decongestant, and antibacterial.

Terpineol—Found in cannabis as well as in over 150 other plants,terpineol exists as four isomers: -terpineol, -terpineol, -terpineol andterpinen-4-ol, are four closely related monoterpene alcohols. These arefound mixed in plants and their essential oils, with -terpineolcomprising the majority of the mixture. The chemical formula is C₁₀H₁₈Oand the four structures are:

Terpineol has a floral aroma, resembling lilacs, clove, citrus, or appleblossoms, and other than cannabis it also occurs naturally in lilacs,pine trees, lime blossoms, and eucalyptus, as well as contributing tothe distinctive, pine smoke-based aroma of lapsang souchong tea. From aflavor perspective, terpineol tastes like mint and anise. Terpineol ismost frequently found in cannabis strains which also contain high levelsof -pinene. Due to -pinene's strong aroma, terpineol may be difficult todetect by odor when the two occur simultaneously as the scent of -pinenemasks the more delicate floral scent of terpineol.

Terpineol, specifically -terpineol, is known to have calming, relaxingeffects and is a mild sedative. Terpineol inhibits skin acne, acts as anantibiotic, anti-inflammatory, antioxidant and has anti-malariaproperties. Terpineol's most important property is its anti-cancerproperty it is able to kill tumors directly.

-Caryophyllene—caryophylene is a bicyclic sesquiterpene with the formulaC₁₅H₂₄ and the structure:

-caryophyllene is found in many plants such as various cannabis strains,Thai basil, cloves, cinnamon leaves and black pepper, oregano, and otheredible herbs; in minor quantities, it may be found in lavender as wellas in many green, leafy vegetables. Its aroma has been described aspeppery, woody spicy, and hoppy, as in hops used for brewing beer, towhich cannabis is closely related.

-caryophyllene is the only terpene known to interact with theendocannabinoid system, and does so at the CB2 receptor, which does notproduce a high (that is, the CB-2 receptor is not implicated in cannabispsychoactivity). -caryophyllene selectively binds to the CB2 receptorwhere it is a functional CB2 agonist, giving it an anxiolytic andanti-depressant effect and showing that -caryophyllene may be useful intreating anxiety and depression. -caryophyllene also has anti-oxidant,anti-inflammatory, anti-cancerous, and local anesthetic effects.Further, -caryophyllene is unique for being both a terpene and a dietarycannabinoid, a food component which acts as a cannabinoid and binds toCB2 receptors.

Other phytocannabinoids in combination, especially cannabidiol (CBD) and-caryophyllene, when delivered orally, appear to be promising candidatesfor the treatment of chronic pain due to their high safety and lowadverse effects profiles.

-caryophyllene, through its CB2 receptor-dependent pathway, may be anexcellent therapeutic agent to prevent nephrotoxicity (poisonous effecton the kidneys) caused by anti-cancer chemotherapy drugs such ascisplatin.

-caryophyllene has antioxidant and antinociceptive (blocks the sensoryneuron detection of pain stimuli) properties. This suggests thathigh-caryophyllene strains may be useful in treating a number of medicalissues such as arthritis and neuropathy pain. It is anti-inflammatorybecause of its ability to bind directly to the endocannabinoid receptorknown as CB2. It is also protective of the cells lining the digestivetract which offers promise for treating some ulcers, and is anti-fungal.-caryophyllene holds promise for cancer treatment.

Linalool—Linalool is a terpene alcohol that occurs as two enantiomersd-linalool and 1-linalool, with the chemical formula C₁₀H₁₈O and thestructures:

Linalool has a floral lavender aroma with a hint of spice. In additionto cannabis, linalool may be found in an array of flowers and spiceplants such as lavender, bay laurel, sweet basil, mint, cinnamon, citrusand even some fungi. Linalool is a critical precursor in the formationof vitamin E.

Linalool may be used as an anti-inflammatory or as an immune booster,and may significantly reduce lung inflammation caused by cigarette smokeas well as reducing lung irritation potentially caused by inhalingcannabis smoke. Linalool helps to restore cognitive and emotionalfunction partially via its anti-inflammatory effect, and may thereforebe used to treat various forms of dementia, and particularly Alzheimer'sdisease. It helps with insomnia, and because it also lessens the anxietybrought on by pure THC, it helps in the treatment of anxiety andpsychosis. Linalool has anesthetic effects and is calming, relaxing andmood lifting, and helps reduce headaches and migraines. Linalool may beuseful to help treat liver cancer, and also helps to modulate motormovements, giving it anti-epileptic properties. It is an effectiveinsecticide against fruit flies, fleas, and cockroaches, making ituseful as an insect repellant and for use in and around the home andgarden.

Limonene—Limonene is a monocyclic monoterpene and one of two majorcompounds formed from pinene. It exists as two enantiomers, d-limoneneand l-limonene, and has the chemical formula C₁₀H₁₆. The structures are:

Limonene has a citrusy aroma and the more common d-isomer smells likeoranges. While it is found in cannabis, it is also present in citrusfruit and especially lemons, juniper, and peppermint. It assists in theabsorption of other terpenes through the skin and other body tissues.Limonene has anti-fungal, anti-bacterial, and anti-depressant effects;it promotes a general uplift in mood and attitude, and it helps promoteweight-loss. It is a strong antioxidant and exerts anti-carcinogenproperties as it may reduce the formation of some tumor growths andalleviate fat buildup in the liver induced by diet. Limonene is known toincrease blood pressure which is useful for those with low bloodpressure. It has very low toxicity and adverse effects are rarelyassociated with it.

Terpinolene—Terpinolene, also called -terpinene (-terpinene), is one ofa class of isomeric monoterpenes, all of which have the chemical formulaC₁₀H₁₆, and which differ from each other only in the position of thecarbon-carbon double bonds. The -terpinene, -terpinene, -terpinene(terpinolene) are all found in plant essential oils, whereas -terpineneis synthetically prepared from sabinene. The chemical structures are:

Terpinolene is characterized by a fresh, piney, floral, herbal,sometimes smoky or woody, and occasionally citrusy aroma and flavor. Itis found in a variety of fragrant plants including cannabis, nutmeg, teatree, conifers, citrus, apples, cumin, marjoram, sage, rosemary,Monterey cypress, and lilacs. It is used in soaps, perfumes, cosmetics,flavorings, and in the semiconductor industries.

Terpinolene is a central nervous system depressant used to inducedrowsiness or sleep or to reduce psychological excitement. It has asedative effect when inhaled, making it useful for insomnia and anxiety.

Terpinolene markedly reduces the expression of the AKT1 gene, whichproduces the protein AKT1 kinase, an enzyme that plays a vital role invarious important signaling pathways and cellular processes. AKT1 kinasehelps regulate cell growth and division (proliferation),differentiation, cell survival, and apoptosis (cell death) when cellsbecome damaged or are no longer needed. The AKT1 gene belongs to theclass of genes known as oncogenes. When mutated, oncogenes have thepotential to cause normal cells to become cancerous. The activation ofAKT is connected with many types of cancers as it increases cellproliferation and suppresses apoptosis. By suppressing the AKT1 geneexpression, both rampant cell proliferation and lack of apoptosis aresuppressed, making terpinolene a valuable anti-cancer agent.

Terpinolene, together with vitamins A and E, prevents the oxidation of“bad cholesterol” (low-density lipoprotein, or LDL) and is thereforehelpful in the treatment of heart disease.

Terpinolene's potential medical benefits include: antioxidant, sedative,antibacterial, antifungal, insect repellent, anti-proliferative(anti-cancer) and non-genotoxic, making it very safe and very healing.

Valencene-Valencene is a bicyclic sesquiterpene with chemical formulaC₁₅H₂₄ and is found in Valencia oranges as well as cannabis The chemicalstructure is:

It has a sweet, fresh, citrusy, woody, aroma and flavor and is used inboth the flavor and perfume industries.

Valencene is toxic to ticks and mosquitoes at lesser concentrations thanDEET and doesn't have the toxicity of DEET. Valencene is an effectiveinsect repellent for ticks, mosquitos, and other insects. It is alsoanti-inflammatory, and may lower the levels of inflammatory markers inmacrophages.

Geraniol-Geraniol is an acyclic monoterpene alcohol whose formula isC₁₀H₁₈O and which boils at about 447° F. and frequently occurs instrains that also produce linalool. Not only from cannabis, geraniol isalso found in rose, geranium, lime, lemon, lemongrass, nutmeg, bergamot,carrot, coriander, lavender, blueberry, blackberry, and tobacco.Geraniol emits a rose-like scent that makes it a popular perfumeadditive. The chemical formula is:

Geraniol is an effective mosquito repellent, an antioxidant, and shows apotential protective effect against neuropathy. It is anti-cancer andinhibits the growth and biosynthesis of colon cancer cells, and whencombined with farnesol and perill alcohol, suppress pancreatic tumorgrowth making it especially useful for cancer of the pancreas whichcurrently is extremely difficult to cure.

Secondary Terpenes:

Phellandrene—Phellandrene refers to a pair of cyclic monoterpenes thathave a similar molecular structure and similar chemical properties,-phellandrene and -phellandrene, which are double-bond isomers of eachother. In -phellandrene, both double bonds are endocyclic (within thering structure) and in -phellandrene, one of them is exocyclic (externalto the ring structure). Phellandrene has the chemical formula C₁₀H₁₆ andis described as pleasant, fresh, citrusy, minty and peppery-woody. Thechemical structures are:

Phellandrenes are used in the perfume and the flavoring industriesbecause of their pleasing aromas and because they are absorbed throughthe skin. -phellandrene may form dangerous, explosive peroxides oncontact with air at elevated temperatures. -phellandrene isnon-hazardous, and both phellandrenes may be found in cannabis as wellas in spices such as allspice, cinnamon, garlic, dill, pepper, parsley,and in the essential oils of angelica, eucalyptus, lavandula, mentha,fennel, ginger, and Pinus species.

Insoluble in water but miscible with ether, phellandrene is one of theeasiest terpenes to identify in the lab. When a solution of phellandrenein a solvent (or an oil containing phellandrene) is treated with aconcentrated solution of sodium nitrate and then with a few drops ofglacial acetic acid, very large crystals of phellandrene nitratespeedily form.

Phellandrene has special medicinal values and has been used intraditional Chinese medicine to treat digestive disorders. It is one ofthe main compounds in turmeric leaf oil, which is used to prevent andtreat systemic fungal infections. Phellandrene possesses antidepressantproperties and is also used as an insecticide.

Carene—3-Carene is a bicyclic monoterpene with a sweet, pungent odor. Itis found naturally in cannabis and in many healthy, beneficial essentialoils, including cypress oil, juniper berry oil and fir needle essentialoils, and is a main constituent of pine and cedar resin. It is alsopresent in bell pepper, basil oil, grapefruit and orange juices, citruspeel oils from fruits like lemons, limes, mandarins, tangerines,oranges, kumquats, and it is a major component of turpentine, comprisingas high as 42% depending on the source. The chemical formula is C₁₀H₁₆and the chemical structure is:

−3-Carene is used as a flavoring in many products.

It is nontoxic, but may cause irritation when inhaled. It is possiblethat high concentrations of −3-carene in some strains may be partlyresponsible for symptoms of coughing, itchy throat, and eye afflictionswhen smoking cannabis

−3-carene is an effective anti-inflammatory. In higher than naturalconcentrations, −3-carene may be a central nervous system depressant anda skin irritant. It is often used to dry out excess body fluids, such astears, runny noses, sweat, and menstrual flows.

Terpinene—Terpinenes are a group of isomeric terpenes with the chemicalformula C₁₀H₁₆ and this group is composed of three natural isomericterpenes and one synthetic one that differ from each other in thepositions of the carbon to carbon double bond. -terpinene, -terpinene(terpinolene), and -terpinene are naturally occurring, whereas-terpinene is not found in nature but may be synthetically produced fromsabinene. -terpinene is also called terpinolene. The chemical structuresare:

Terpinene is a major component of essential oils made from citrusfruits, and has a lemon odor. -terpinene is widely used in the flavor,perfume, cosmetics, soap, pharmaceutical industries, as well as in foodand confectionary.

Terpinene is considered to be a well-tolerated additive in thepharmaceutical industry, and it has very strong antioxidant properties.

Fenchol-Fenchol, also called 1,3,3-trimethyl-2-norbornanol, is a terpeneand an isomer of borneol with the chemical formula C₁₀H₁₈O and thechemical formula is:

This particular terpene is an enantiomer, d-fenchol or(1R)-endo-(+)-fenchol, but it has no mirror image found in nature, thusit is enantiopure.

Found in cannabis, it also occurs naturally in basil, fennel, nutmeg,pine, rosemary oil, lime oil, beer and more. It has a bitter, limeflavor and is used extensively in perfumes, flavorings, soaps,detergents, and personal care products. It is known to exhibitantibacterial properties.

Borneol—Borneol, a terpene alcohol, has the chemical formula C₁₀H₁₈O andexists naturally as two enantiomers, l-borneol and d-borneol, both ofwhich are found in nature. It is easily oxidized to camphor, has anaroma of camphor, mint, and earth, and is a component of many naturalessential oils. It is found in cannabis resin and herbs like thyme,rosemary, and cinnamon. The chemical structure is:

Borneol is used in the perfume industry, as well as in dietary andherbal supplements in the USA.

Borneol is used as a calming sedative, it is used to fight fatigue,stress, to relax, and to recover from illness. Borneol is used as ananti-inflammatory, an anti-nociceptive/analgesic, a skin tonic, a localanesthetic, as an anti-insomnia, anti-septic, a digestive aid, asedative and an antispasmodic. It is used to improve circulation, toreduce pain and swelling, as a bronchodilator, a cough suppressant, andan insect repellant.

Bisabolol—Also called levomenol, -bisabolol is a natural monocyclicunsaturated sesquiterpene alcohol with the chemical formula C₁₅H₂₆O anda chemical structure of:

-bisabolol is found in cannabis, the Brazilian shrub candeia, and Germanchamomile. It has a floral aroma.

-bisabolol, which is nontoxic and nonirritating to the skin, possessesanti-inflammatory and wound healing properties, as well as antimycoticand antibacterial effects, and may be used as a deodorizer. It is apotent inhibitor of fungi, Candida albicans, and gram-positive bacteria.It shows promise in the treatment of certain cancers as it inducesapoptosis in leukemia.

Phytol—Phytol is a natural linear diterpene alcohol with the chemicalformula C₂₀H₄₀O that may be used as a precursor to prepare syntheticforms of vitamin E and vitamin K1. Found in cannabis and green tea,phytol results from the degradation of chlorophyll and is an oily liquidthat is nearly insoluble in water, but soluble in most organic solvents.The chemical structure is:

Phytol inhibits the enzyme that degrades the neurotransmitter GABA(-aminobutyric acid), which may partially account for its relaxingeffect. In the body, phytol is essential in activating enzymes that havea positive effect on the production of insulin. It is beneficial inregulating blood glucose, for reducing blood pressure and for reducingcholesterol levels in blood.

Camphene—Camphene is a bicyclic monoterpene with the chemical formulaC₁₀H₁₆ and the chemical structure:

Camphene readily volatilizes at room temperature and has a pungent odorsimilar to camphor. It is a minor component of many essential oils suchas turpentine, cypress, neroli, valerian camphor, citronella and ginger.It is used as a flavoring for food, and in the perfume industry. It isproduced industrially by catalytic isomerization of the more common-pinene.

Camphene is found in essential oils extracted from cannabis and certaintrees, and it may play a critical role in cardiovascular health.Camphene possesses antioxidant, anti-inflammatory, and antibioticcharacteristics, and shows promise for pain relief.

Camphene may reduce plasma cholesterol and triglycerides. Given theimportance this plays in heart disease, camphene might be used as analternative to pharmaceutical drugs which cause intestinal problems,liver damage, and muscle inflammation.

Sabinene—Sabinene is a bicyclic monoterpene with the chemical formulaCH, and exists as d and l enantiomers. The chemical structures are:

It has an aroma of spice, pine, and orange, and is found in many plantsincluding cannabis, Norway spruce, black pepper, basil, and Myristicafragrans the world's main source of nutmeg. It is used in the perfumeindustry and in the food industry as a flavoring.

Sabinene has antioxidant and anti-inflammatory properties, and benefitsliver function, digestion, relieves arthritis, and may soothe skinconditions.

Camphor—Camphor is a waxy, flammable, white crystalline solid with thechemical formula CHO. Camphor occurs naturally as d-camphor, thel-enantiomer being synthetically produced.

It is commonly found in cannabis, rosemary leaves, camphor basil, and inCinnamomum camphora, which goes by several common names includingcamphor tree, camphorwood, and camphor laurel. Camphor is also found inkapur trees, and a few other related trees in the laurel family, notablyOcotea usambaensis.

The ancient Egyptians used camphor as one of the ingredients used formummification. It has been used as an ingredient in sweet and savoryfoods in medieval Europe and Arabia. Camphor is readily absorbed throughthe skin, and when applied topically produces a cooling sensationsimilar to that of menthol. It acts as a slight local anesthetic,relieves pain, itching and swelling, and has antimicrobial properties.It is used as a cough suppressant, a decongestant, an insect repellantnotably for cockroaches and fleas, and is used to make mothballs.Camphor has been used to treat sprains, swellings, inflammation, andfevers. In very small quantities taken internally, it is used to treatminor heart symptoms and fatigue. Camphor increases heart rate, is askin vasodilator, and reduces appetite.

Isoborneol—Isoborneol is a bicyclic terpene alcohol with the chemicalformula C₁₀H₁₈O and the chemical structure:

Isoborneol is a waxy solid with an odor similar to that of camphor, andis found in cannabis and mugwort. Isoborneol exhibits antiviralproperties and is a potent inhibitor of herpes simplex virus type 1.Besides being antiviral, it also has antioxidant, anti-inflammatory, andantimicrobial properties.

Menthol—Menthol is a terpene alcohol with the chemical formula C₁₀H₂₀Oand the chemical structure:

Menthol is found in cannabis and in members of the mint family such ascorn mint and peppermint. Menthol is a white or colorless crystallinesolid at room temperature. It is used in candies, cigarettes, cosmetics,personal care products, and medicines.

Menthol produces a cooling sensation on the skin and soft tissues of themouth by activating the TRPM8 receptor protein that senses the change intemperature in cold-sensing nerves. However, menthol gives a coolsensation without any actual fall in temperature in that area. Thislowers inflammation in the area, causing the nearby blood vessels todilate, and increases blood flow to the area which delivers freshnutrients to repair the area and removes any toxic wastes generated.This process speeds healing. Menthol may also bind to another receptorcalled kappa opioid receptor that may also produce a numbing effect.

Menthol exhibits analgesic properties and is used topically to treatinflammatory pain caused by conditions such as arthritis, bursitis,tendonitis, muscle strains or sprains, backache, bone pain, bruising,and cramping.

Menthol cigarettes have a lower cancer risk and cause far less cigaretterelated cancers than their non-mentholated counterparts, making mentholan important and possibly mitigating component of inhaled cannabis.

Cedrene—Cedrene is a sesquiterpene with the chemical formula C₁₅H₂₄ andexists in two isomeric forms, -cedrene and -cedrene, which differ in theposition of one double bond.

Cedrene is a light yellowish transparent oil with the aroma of cedarwood and is found in cannabis, fenugreek, and in the essential oil ofcedar.

Cedrene possesses antiseptic, antimicrobial, antifungal, and anticancerproperties, particularly against T-cell lymphoma, which may occur in theblood as leukemia or in lymph nodes (lymphoma), skin, or other areas ofthe body.

Nerolidol—Also known as peruviol, nerolidol is a naturally occurringsesquiterpene alcohol present in various plants with a floral odor, andhas the chemical formula C₁₅H₂₆O. It exists in two isomeric forms, cisand trans, which differ in their geometry about the central double bond.The chemical structures are:

Nerolidol has a floral, citrus, woody, fresh bark aroma, and may befound in Cannabis sativa, neroli, niaouli, ginger, jasmine, lavender,tea tree, citronella, lemon grass, and Brassavola nodosa, a Mexicanorchid.

Nerolidol is widely used in perfumes as both a base note fragrancecomponent and as a fixative; it is also used in cosmetics, personal careproducts, detergents and cleaning products, and as a food flavoringagent.

It has anti-fungal, anti-leishmaniasis (an infection caused by protozoanLeishmania parasites, which are spread by the bite of phlebotomine sandflies) and anti-malarial properties. It also produces a sedative effect.It may enhance skin penetration for the transdermal delivery oftherapeutic drugs.

Guaiol—Guaiol, also called champacol, is a sesquiterpenoid alcohol foundin several plants, including Cannabis indica, guaiacum and cypress pine.It is a crystalline solid at room temperature with the chemical formulaC₁₅H₂₆O and the structure:

Guaiol has a woody, rosy, floral aroma. Cannabis strains known tocontain guaiol include Liberty Haze, Blue Kush, Chocolope, and MedicalMass.

Guaiol has been used for centuries as a treatment for diverse ailmentsranging from coughs to constipation to arthritis and syphilis. It isalso an effective insect repellent and insecticide. Guaiol's potentialmedical properties include: Antimicrobial, Anti-inflammatory, laxative,diuretic, and insect repellant.

Isopulegol—Isopulegol is a monoterpene alcohol found in cannabis, cornmint, European pennyroyal, lemongrass and geranium, and possesses aminty aroma. It has the chemical formula C₁₀H₁₈O and the structure:

Isopulegol is used as a flavoring agent in food, in cosmetics, and inperfumes, personal care products, and cleaners. It is a chemicalprecursor to menthol, and shows many promising routes for therapeuticuse. Isopulegol possesses gastroprotective, anti-convulsive,anti-inflammatory, antioxidant, and stress-reducing effects, and itreduces the severity of seizures and anxiety in animal models.

Geranyl Acetate—Geranyl acetate has several other names includinggeraniol acetate, and is a monoterpene ester with a sweet, strong,floral rose and fruity aroma. It is a colorless liquid at roomtemperature and has the chemical formula C₁₂H₂₀O₂ with the structure:

It is used in the fragrance and flavor industries, and is found inproducts such as soaps, detergents, personal care products, fabricsofteners, and as a middle note in perfumes.

Geranyl acetate is found in a variety of natural essential oils, such ascannabis, citronella, palmarosa, geranium, coriander, neroli,lemongrass, petitgrain, carrot, sassafras, rose, and many others. Itexhibits strong antimicrobial, antifungal, and anti-inflammatoryeffects.

Cymene—Also called p-cymene, para-cymene, methyl-isopropyl-benzene, andl-isopropyl-4-methylbenzene among others, this aromatic, parasubstituted benzene ring is an alkylbenzene monoterpene with the formulaC₁₀H₁₄ and the structure:

The other two isomers of methyl-isopropyl-benzene are o-cymene(orthocymene) and m-cymene (meta cymene), however only p-cymene is anaturally occurring compound. It has a citrusy-woody-spicy odor withherbal hints, and is found in cumin, thyme, anise, coriander, mace,oregano, eucalyptus and in angelica root and angelica seed oil, bay leafoil, basil oil, carrot seed oil, clove bud oil, clary sage oil, andgrape fruit oil. It is used in flavoring beverages, cakes andconfectionery, as well as in the fragrance, paint, and furnitureindustries.

P-cymene has documented anti-inflammatory effects, it shows potentialprotective effects against acute lung injury, and is effective againstpathogenic bacteria, especially Escherichia coli. When combined withcarvacrol it is also antibacterial and possibly even more so.P-carvacrol, thymol and p-cymene work synergistically together and haveanti-fungal properties; p-cymene by itself showed strong antifungalactivity against numerous candida species. P-cymene also showsanti-inflammatory, antinociceptive and analgesic properties.

Eucalyptol—Eucalyptol has many other names, including 1,8-cineol,cajeputol; 1,8-epoxy-p-menthane, and eucalyptole. Eucalyptol is a cyclicmonoterpenoid ether and it is the main component of eucalyptus essentialoil having the chemical formula C₁₀H₁₈O and the chemical structure:

Eucalyptol has a minty, earthy, spicy aroma and is found in severalplants including Cannabis sativa, camphor laurel, bay leaves, tea tree,mugwort, sweet basil, wormwood, rosemary, common sage, and otheraromatic plants. Eucalyptol is used in flavorings in baked goods,confectionery, meat products, beverages, and mouth wash; in fragrances,cigarettes and cosmetics.

Eucalyptol has many medicinal uses, it relieves pain, suppresses coughs,and improves concentration and inner balance. Plants containingeucalyptol enhance meditation and concentration. Eucalyptol has potentantifungal effects and is used as an insecticide and insect repellent.Eucalyptol inhibits cytokine production in lymphocytes and monocytes,giving it an anti-inflammatory effect, and it reduces inflammation andpain when applied topically. It is able to kill in vitro leukemia cellsof two cultured leukemia cell lines. Eucalyptol is effective forcontrolling asthma and reduces airway mucus hypersecretion by itsanti-inflammatory cytokine inhibition, and it is an effective treatmentfor nonpurulent rhinosinusitis.

Pulegone—Pulegone, a monocyclic monoterpenoid, is a secondary terpenecomponent of cannabis. It exists naturally in two enantiomeric forms,d-pulegone and l-pulegone, with d-pulegone being the most abundant. Thechemical formula is C₁₀H₁₆O and the structure is:

It has an aroma of peppermint and camphor, and it is found in severalplants besides cannabis, such as catnip, peppermint, spearmint,pennyroyal, and rosemary. It is used for flavoring foods, drinks, anddental products, as a spice, it is used as fragrance components indetergents and cosmetics, it is used in herbal medicines, perfumery, andaromatherapy.

Pulegone is an emmenagogue, a mucolytic, and is good for congestion ofthe respiratory system. Pulegone may have significant sedative andfever-reducing properties. It may also alleviate the side effects ofshort-term memory loss sometimes associated with higher levels of THC.Pulegone is a powerful insecticide.

Traditionally, plants containing pulegone, such as pennyroyal, have beenused as herbal teas for non-ulcer dyspepsia, primary dysmenorrhoea,secondary amenorrhoea and oligomenorrhoea, as an abortifacient, and as adiaphoretic. Pennyroyal essential oil has been used for the sameconditions. Pulegone is a hepatotoxic (liver poison) and nephrotoxic(kidney poison) constituent of the folklore abortifacient pennyroyaloil.

Today, Mentha piperita (peppermint) and Mentha pulegium (pennyroyal) areused for colds, headache, migraine, as a diuretic, antispasmodic,anticonvulsive, anti-emetic, heart stimulant, sedative, and to treat thesymptoms of inflammatory bowel syndrome. Rosemary inhibitsacetylcholinesterase in the brain yielding more acetylcholine andallowing nerve cells to communicate more effectively with one another,giving promise for treatment of memory issues and dementias.

One other terpene found in cannabis that bears mentioning is humulene.

Humulene—Humulene is a monocyclic sesquiterpene containing an11-membered ring and is also known as -humulene and -caryophyllene (anisomer of -caryophyllene). Humulene is often found in combination withit's isomer, -caryophyllene, it has the chemical formula C₁₅H₂₄ and thestructure is:

Humulene is found in Cannabis sativa strains, hops and Vietnamesecoriander, pine trees, orange trees, marsh elders, tobacco, sage,ginseng, ginger, and sunflowers, among other plants. Humulene is whatgives beer its distinct “hoppy” aroma, and also contributes to the samehoppy aroma in cannabis.

Humulene is anti-tumor, anti-bacterial, is a strong anti-inflammatory,and is anorectic (suppresses appetite). It is often blended with-caryophyllene and used as a potent remedy for inflammation. Humuleneaids in weight loss by acting as an appetite suppressant.

In the body, terpenes act on receptors and neurotransmitters. Theyreadily combine with, or dissolve in, lipids or fats. Terpenes may actas serotonin uptake inhibitors, they may enhance norepinephrineactivity, they may increase dopamine activity, and they may augmentsynaptic -aminobutyric acid (GABA) levels by inhibiting re-uptake. Theseactions are similar to many of the commonly prescribed anti-depressantdrugs used today

The differences in the amounts and types of both cannabinoids andterpenes, along with the other lesser compounds within the cannabisvarieties, imbue the various cannabis extracts with medicinalsignificance. Adding or increasing one or more of these compounds canalter the effects of cannabis extract, as certain compounds work insynergy to augment desirable effects while other compounds act asantagonists to inhibit undesirable effects.

Cannabis has been used to treat pain since at least the third millenniumBC. In recent decades, and especially since changes in state lawsallowing medical use of cannabis, there has developed a substantial bodyof anecdotal evidence that cannabis, particularly smoked cannabis plantmatter, provides substantial relief from chronic pain caused by numerouschronic health conditions such as cancer, multiple sclerosis, arthritis,nerve damage, back pain, fibromyalgia, and similar conditions. In fact,smoked cannabis plant matter appears to be a preferred method of paintreatment by those with chronic medical conditions, even though otherforms of administration of cannabis are available for medical use. Thispreference is likely due to a variety of factors. First, smokingcannabis allows the user to easily control the dosage, as the effectsare felt quickly, and additional amounts can be smoked if the initialeffects are insufficient. Second, the concentrations of active cannabiscompounds in the bloodstream are high compared to oral administration,and more powerful, as the active cannabis compounds go directly into thebloodstream instead of being processed into other compounds by theliver. Third, the combined effect of the dozens of cannabis compounds incannabis plant matter may provide a more pleasant subjective effect, orother benefits such as reduced inflammation, beyond that of a purifiedcannabinoid medical product. In an aspect of the embodiment, cannabiscompounds can be selected in formulations designed to specifically toaddress each of these issues, while avoiding the detriments of smokedcannabis plant matter, such as respiratory irritation and the increasedpotential for lung disease. Further arguing in favor ofspecifically-formulated cannabis-based products is the fact that certainmodern North American and European strains of cannabis displayrelatively high concentrations of THC (a potent psychoactive compound),but relatively little CBD or other phytocannabinoid content.

A substantial body of medical literature supports the anecdotal evidencethat cannabis can be used to treat chronic pain. The endocannabinoidsystem is active in the control of pain. Compounds found in cannabis acton the endocannabinoid system, and certain of these compounds have apowerful analgesic effect. For example, THC is believed to be ten timesmore powerful than morphine in mediating pain in wide dynamic rangeneurons in the ventroposterolateral nucleus of the thalamus. Cannabidiol(CBD) is also believed to have strong analgesic effects, due to itsfunction as an endocannabinoid modulator, likely through its ability topromote signaling of the adenosine receptor A2A by inhibiting theadenosine transporter. Cannabigerol (CBG), a “minor cannabinoid” foundin small quantities in cannabis, is believed to have even greateranalgesic activity than THC.

Chronic pain conditions are often resistant to standard treatments,including treatment with opioid medications such as morphine. There issome medical evidence that suggests that cannabinoids are complementaryto treatment with opioids, offering additional pain reduction on top ofthat provided by the opioids. Combining cannabis treatments for chronicpain with opioid treatments for chronic pain may have the benefit ofreducing patient pain levels, reducing reliance on (and addiction to)opioids, or both.

The inventor has conceived, and reduced to practice, a variety ofcannabis formulations for the treatment of chronic pain. In oneexemplary aspect of the embodiment, different combinations of THC, CBD,and CBG may be used to obtain the desired amount of pain relief due tochronic illnesses. In another exemplary aspect of the embodiment,different combinations of THC, CBD, and CBG may be used to complementand enhance opioid pain treatments, and to manage pain while reducingdependence on opioids.

The inventor has also conceived, and reduced to practice, a variety ofcannabis formulations for the delivery of an enhanced cannabinoid effectemploying the terpene myrcene. This not only raises the saturation levelof a predominant cannabinoid receptor such as CB1 for cannabinoids suchas THC, but also increases permeability of the cell membrane anddecreases the resistance across the blood-brain barrier for medicinalcompounds known to be present in cannabis extracts, thus potentiatingthe effects of these medically effective compounds at several majorsites of action.

In one exemplary aspect of the embodiment, the formulation to treatsleep disorders may be: 5 mg-9-tetrahydrocannabinol (THC), 5 mgcannabidiol (CBD), and 5 mg cannabigerol (CBG). The combined mixture maybe compounded into a liquid form for inhalation using a vaporizer.

In another aspect of the embodiment, the terpene myrcene will be addedto the formulation to raise the saturation level of a predominantcannabinoid receptor such as CB1 for cannabinoids such as THC, increasepermeability of the cell membrane, and decrease the resistance acrossthe blood-brain barrier for medicinal compounds known to be present incannabis extracts, thus potentiating the effects of these medicallyeffective compounds at several major sites of action.

One or more different formulations may be described in the presentapplication. Further, for one or more of the formulations describedherein, numerous alternative embodiments may be described. It should beunderstood that these are presented for illustrative purposes only; thedescribed embodiments are not intended to be limiting in any sense. Ingeneral, embodiments are described in sufficient detail to enable thoseskilled in the art to practice one or more of the formulations, and itis to be understood that other embodiments may be utilized and thatstructural, compound constituent, constituent compound ratio,constituent compound isomer, constituent compound concentration andother changes may be made without departing from the scope of theparticular formulations. When an active compound with multiple naturallyoccurring isomers is cited, it is to be understood that a mixturecontaining concentrations of those isomers as are found in nature incannabis is in use unless otherwise specified. Accordingly, thoseskilled in the art will recognize that one or more of the formulationsmay be practiced with various modifications and alterations. Particularfeatures of one or more of the formulations may be described withreference to one or more particular embodiments or figures that form apart of the present disclosure, and in which are shown, by way ofillustration, specific embodiments of one or more of the formulations.It should be understood, however, that such features are not limited tousage in the one or more particular embodiments or figures withreference to which they are described. The present disclosure is neithera literal description of all embodiments of one or more of theformulations nor a listing of features of one or more of theformulations that must be present in all embodiments.

Cannabinoids, terpenes and flavonoids employed in aspects are to beassumed isolated and purified by previously published means best suitedfor that active compound which may include but are not limited to HPLC,also known as high pressure liquid chromatography, distillation,fractional distillation, steam distillation, supercritical fluidextraction, either with or without additional, modifying solvents aswell as other methods known to those skilled in the art.

When single cannabinoids, multiple cannabinoid mixtures,cannabinoid-terpene mixtures, cannabinoid-terpene-flavonoid, terpene,multiple terpene and terpene-flavonoid mixtures are listed inembodiments, they are to be assumed administered by methods previouslycited to both retain the stability of all active compounds cited in aformulation and to effect delivery of all active compounds within theformulation. These delivery methods may comprise, but are not limitedto, administering the orally, anally, or via injection compoundscontaining a known amount of the formulation, inhalation of vaporcomprising the formulation, administration of sublingual tinctures ofthe formulation, extracts of the formulation, oils of the formulation,capsules of the formulation and tablets of the formulation as well asother administrative methods known to be applicable to those withordinary skill in the art.

It will be readily apparent that more than one method of administrationmay be used for delivery of a single formulation cited in an embodiment,and that any method of administration that maintains both constituentactive compound stability and high bioavailability of each activecompound may be employed for a single cited formulation.

Techniques and mechanisms described or referenced herein will sometimesbe described in singular form for clarity. However, it should be notedthat particular embodiments include multiple iterations of a techniqueor multiple manifestations of a mechanism unless noted otherwise.

DETAILED DESCRIPTION OF EXAMPLES

FIG. 1 is a method diagram illustrating a process 100 for preparingcannabis medicinal products, according to a preferred aspect. Theoverall process of creating medicinal products from the cannabis plantconsists of six stages: cultivation 101, extraction 102, concentration103, separation 104, secondary concentration 105, and processing 106. Atthe cultivation stage 101, the cannabis plants are grown and harvested.The harvested plant matter, or selected portions of it, is sent forextraction 102, at which point essential oils of the plant areextracted, which contain some plant matter in the form of chlorophyll,plant waxes, plant lipids, plus substantial amounts of cannabinoids,terpenes, and flavonoids. These oils are concentrated 103 viaevaporation. In the separation stage 104, the cannabis compounds areseparated from the concentrated oils via a variety of processingmethods, usually involving high pressure liquid chromatography or flashchromatography. At this stage, the purified cannabis compounds(cannabinoids, terpenes, and flavonoids) are sent for furtherconcentration 105 via evaporation. Said concentrated, purified cannabiscompounds are then processed 106 with other ingredients to createmedicinal products, for example pills, tablets, salves, injectables,etc.

In an aspect, additional amounts of the terpene myrcene is added to theproduct in step 106 to take advantage of the unique advantages presentedby -myrcene, which is shown to increase the permeability of the cellmembrane, decrease the resistance across the blood-brain barrier, andincrease saturation at the CB1 receptor site for a plurality ofcompounds including itself, other terpenes, and cannabinoids includingbut not limited to THC. For example, infusing myrcene as well as THCinto the product in step 106 may ensure that THC's (or, for othertherapeutic effects, cannabinoids such as CBD, CBN, or CBG) maximalactivation level may be increased by a biologically significant amount,and that increase may be achieved at a faster rate. Formulationsincluding selected THC, other cannabinoids and terpenes in the presenceof myrcene may significantly augment the efficacy of such formulationsfor the desired biological and medicinal effects. One analgesic andanti-inflammatory formulation may be: 0.30% w/w to 50% -myrcene, 20% w/wto 35% w/w cannabidiol (CBD), 10% w/w to 25% w/w -pinene, 5% w/w to 15%w/w terpineol, and 10% w/w to 30% borneol. Another myrcene-enhancedanalgesic and anti-inflammatory formulation may be 0.25% w/w to 40% w/w-myrcene, 10% w/w to 20% w/w cannabidiol (CBD), 5% w/w to 15% w/wp-cymene and 15% w/w to 30% borneol.

FIG. 2 is a method diagram illustrating a process 200 for preparing anenhanced smokable therapeutic cannabis product using hash resin,according to a preferred embodiment. The inventors have discovered, inparticular, that using the methods described herein rather than, as iscommonly done in the art, infusing smokable plant material directly withhash resin, provides a superior product that tastes better, smokes moresmoothly, and has predictable therapeutic effects (which may in fact bevaried, according to aspects of the invention, by varying thecannabinoid profile of the oil used to spray plant matter in step 206,as described below). According to a preferred aspect, dried cannabisplant matter is treated to separate hash resin 201, as is known in theart, and the remaining plant matter is further dried until it issubstantially moisture-free 202. In another step, the hash resin ispressed to expel oils 203 (which are used for other purposes); it willbe appreciated by those having ordinary skill in the art that theresulting oil will be very rich in cannabinoids and terpenes (as well asflavonoids), as described above. Further, the pressed hash resin istreated with an oil rich in medium-chain triglycerides (MCT oil) 204,which extracts a substantial amount of THC and other cannabinoids; thisMCT-based, THC-infused oil represents a recovered fraction of the THCpresent in the hash resin. The THC-infused MCT oil may be furtherenriched 205 by addition of pure P myrcene and other desiredcannabinoids, terpenes, and flavonoids as desired (for differentaspects, different cannabinoid profiles may be used to enrich theTHC-infused MCT oil, depending on the desired therapeutic effect).

According to a preferred aspect, the terpene myrcene is added to MCT oil205 to take advantage of the unique advantages presented by (-myrcene,which is shown to increase the permeability of the cell membrane,decrease the resistance across the blood-brain barrier, and increasesaturation at the CB1 receptor site for a plurality of compoundsincluding itself, other terpenes, and cannabinoids including but notlimited to THC. For example, infusing myrcene as well as THC into theMCT oil prior to spraying dried, smokable cannabis plant matter 205 mayensure that THC's (or, for other therapeutic effects, cannabinoids suchas CBD, CBN, or CBG) maximal activation level may be increased by abiologically significant amount, and that increase may be achieved at afaster rate. Formulations including selected THC, other cannabinoids andterpenes in the presence of myrcene may significantly augment theefficacy of such formulations for the desired biological and medicinaleffects.

A person with ordinary skill in the art will be aware of a range ofpossible modifications of the various embodiments described above.Accordingly, the present invention is defined by the claims and theirequivalents.

What is claimed is:
 1. A method of preparing a cannabis-basedtherapeutic product for the treatment of chronic pain, the methodcomprising the steps of: (a) separating hash resin from plant materialof a cannabis plant of a specific strain; (b) pressing the hash resin toexpel oil, leaving spent hash resin; (c) extracting further cannabinoidsfrom the spent hash resin using MCT oil; (d) separating the cannabiscompounds from the oils using high pressure liquid chromatography orflash chromatography; (e) mixing cannabis compounds obtained via steps(a)-(d) from one or more strains of cannabis to obtain a formulationtherapeutically-effective for use in treating chronic pain; and (f)processing the formulation from step (e) into a pill or tablet suitablefor therapeutic administration to a human patient; wherein theformulation comprises at least 5% w/w β-myrcene, between 20% w/w and 35%w/w cannabidiol, at least 10% α-pinene, at least 5% w/w terpineol, andat least 10% w/w borneol.
 2. The method of claim 1, wherein theformulation further comprises at least 5% w/w p-cymene.
 3. Acannabis-based treatment product for chronic pain produced according tothe method of claim
 1. 4. A cannabis-based treatment product for chronicpain produced according to the method of claim 2.